Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OT8490HT)

• DOT Name: Low-density lipoprotein receptor-related protein 10 (LRP10)
• Synonyms: LRP-10
• Gene Name: LRP10
• Related Disease:
  Lewy body dementia
  Parkinson disease
  Abdominal aortic aneurysm
  Alzheimer disease
  Neuroblastoma
  Hepatocellular carcinoma
  Pancreatic adenocarcinoma
  Dementia
• UniProt ID: LRP10_HUMAN
• Pfam ID: PF00431 ; PF00057
• Sequence:
  MLLATLLLLLLGGALAHPDRIIFPNHACEDPPAVLLEVQGTLQRPLVRDSRTSPANCTWL
  ILGSKEQTVTIRFQKLHLACGSERLTLRSPLQPLISLCEAPPSPLQLPGGNVTITYSYAG
  ARAPMGQGFLLSYSQDWLMCLQEEFQCLNHRCVSAVQRCDGVDACGDGSDEAGCSSDPFP
  GLTPRPVPSLPCNVTLEDFYGVFSSPGYTHLASVSHPQSCHWLLDPHDGRRLAVRFTALD
  LGFGDAVHVYDGPGPPESSRLLRSLTHFSNGKAVTVETLSGQAVVSYHTVAWSNGRGFNA
  TYHVRGYCLPWDRPCGLGSGLGAGEGLGERCYSEAQRCDGSWDCADGTDEEDCPGCPPGH
  FPCGAAGTSGATACYLPADRCNYQTFCADGADERRCRHCQPGNFRCRDEKCVYETWVCDG
  QPDCADGSDEWDCSYVLPRKVITAAVIGSLVCGLLLVIALGCTCKLYAIRTQEYSIFAPL
  SRMEAEIVQQQAPPSYGQLIAQGAIPPVEDFPTENPNDNSVLGNLRSLLQILRQDMTPGG
  GPGARRRQRGRLMRRLVRRLRRWGLLPRTNTPARASEARSQVTPSAAPLEALDGGTGPAR
  EGGAVGGQDGEQAPPLPIKAPLPSASTSPAPTTVPEAPGPLPSLPLEPSLLSGVVQALRG
  RLLPSLGPPGPTRSPPGPHTAVLALEDEDDVLLVPLAEPGVWVAEAEDEPLLT
• Function: Probable receptor, which is involved in the internalization of lipophilic molecules and/or signal transduction. May be involved in the uptake of lipoprotein APOE in liver.
• Tissue Specificity: Expressed in blood leukocyte, lung, placenta, small intestine, liver, kidney, spleen, thymus, colon, skeletal muscle and heart.
• Reactome Pathway: Retinoid metabolism and transport (R-HSA-975634)

Molecular Interaction Atlas (MIA) of This DOT

8 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Lewy body dementia	DISAE66J	Definitive	Genetic Variation	[1]
Parkinson disease	DISQVHKL	Definitive	Biomarker	[1]
Abdominal aortic aneurysm	DISD06OF	Strong	Genetic Variation	[2]
Alzheimer disease	DISF8S70	Strong	Biomarker	[3]
Neuroblastoma	DISVZBI4	Strong	Altered Expression	[3]
Hepatocellular carcinoma	DIS0J828	moderate	Altered Expression	[4]
Pancreatic adenocarcinoma	DISKHX7S	moderate	Altered Expression	[4]
Dementia	DISXL1WY	Limited	Genetic Variation	[1]

1 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate increases the methylation of Low-density lipoprotein receptor-related protein 10 (LRP10).	[5]

21 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Ciclosporin	DMAZJFX	Approved	Ciclosporin increases the expression of Low-density lipoprotein receptor-related protein 10 (LRP10).	[6]
Tretinoin	DM49DUI	Approved	Tretinoin increases the expression of Low-density lipoprotein receptor-related protein 10 (LRP10).	[7]
Acetaminophen	DMUIE76	Approved	Acetaminophen decreases the expression of Low-density lipoprotein receptor-related protein 10 (LRP10).	[8]
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate increases the expression of Low-density lipoprotein receptor-related protein 10 (LRP10).	[9]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Low-density lipoprotein receptor-related protein 10 (LRP10).	[10]
Quercetin	DM3NC4M	Approved	Quercetin increases the expression of Low-density lipoprotein receptor-related protein 10 (LRP10).	[11]
Temozolomide	DMKECZD	Approved	Temozolomide decreases the expression of Low-density lipoprotein receptor-related protein 10 (LRP10).	[12]
Calcitriol	DM8ZVJ7	Approved	Calcitriol increases the expression of Low-density lipoprotein receptor-related protein 10 (LRP10).	[13]
Testosterone	DM7HUNW	Approved	Testosterone increases the expression of Low-density lipoprotein receptor-related protein 10 (LRP10).	[13]
Marinol	DM70IK5	Approved	Marinol increases the expression of Low-density lipoprotein receptor-related protein 10 (LRP10).	[14]
Demecolcine	DMCZQGK	Approved	Demecolcine increases the expression of Low-density lipoprotein receptor-related protein 10 (LRP10).	[15]
Niclosamide	DMJAGXQ	Approved	Niclosamide increases the expression of Low-density lipoprotein receptor-related protein 10 (LRP10).	[16]
Azathioprine	DMMZSXQ	Approved	Azathioprine increases the expression of Low-density lipoprotein receptor-related protein 10 (LRP10).	[17]
Clozapine	DMFC71L	Approved	Clozapine increases the expression of Low-density lipoprotein receptor-related protein 10 (LRP10).	[18]
Benzo(a)pyrene	DMN7J43	Phase 1	Benzo(a)pyrene increases the expression of Low-density lipoprotein receptor-related protein 10 (LRP10).	[6]
(+)-JQ1	DM1CZSJ	Phase 1	(+)-JQ1 decreases the expression of Low-density lipoprotein receptor-related protein 10 (LRP10).	[19]
Bisphenol A	DM2ZLD7	Investigative	Bisphenol A affects the expression of Low-density lipoprotein receptor-related protein 10 (LRP10).	[20]
Trichostatin A	DM9C8NX	Investigative	Trichostatin A increases the expression of Low-density lipoprotein receptor-related protein 10 (LRP10).	[21]
Formaldehyde	DM7Q6M0	Investigative	Formaldehyde increases the expression of Low-density lipoprotein receptor-related protein 10 (LRP10).	[15]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Low-density lipoprotein receptor-related protein 10 (LRP10).	[22]
Sulforaphane	DMQY3L0	Investigative	Sulforaphane increases the expression of Low-density lipoprotein receptor-related protein 10 (LRP10).	[23]

References

• [1] LRP10 in autosomal-dominant Parkinson's disease.Mov Disord. 2019 Jun;34(6):912-916. doi: 10.1002/mds.27693. Epub 2019 Apr 9.
• [2] LRP10 genetic variants in familial Parkinson's disease and dementia with Lewy bodies: a genome-wide linkage and sequencing study.Lancet Neurol. 2018 Jul;17(7):597-608. doi: 10.1016/S1474-4422(18)30179-0. Epub 2018 Jun 7.
• [3] LDLR-related protein 10 (LRP10) regulates amyloid precursor protein (APP) trafficking and processing: evidence for a role in Alzheimer's disease.Mol Neurodegener. 2012 Jun 26;7:31. doi: 10.1186/1750-1326-7-31.
• [4] Expression of LDL receptor-related proteins (LRPs) in common solid malignancies correlates with patient survival.PLoS One. 2017 Oct 31;12(10):e0186649. doi: 10.1371/journal.pone.0186649. eCollection 2017.
• [5] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [6] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.
• [7] Development of a neural teratogenicity test based on human embryonic stem cells: response to retinoic acid exposure. Toxicol Sci. 2011 Dec;124(2):370-7.
• [8] Gene expression analysis of precision-cut human liver slices indicates stable expression of ADME-Tox related genes. Toxicol Appl Pharmacol. 2011 May 15;253(1):57-69.
• [9] Physiological and toxicological transcriptome changes in HepG2 cells exposed to copper. Physiol Genomics. 2009 Aug 7;38(3):386-401.
• [10] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [11] Comparison of phenotypic and transcriptomic effects of false-positive genotoxins, true genotoxins and non-genotoxins using HepG2 cells. Mutagenesis. 2011 Sep;26(5):593-604.
• [12] Temozolomide induces activation of Wnt/-catenin signaling in glioma cells via PI3K/Akt pathway: implications in glioma therapy. Cell Biol Toxicol. 2020 Jun;36(3):273-278. doi: 10.1007/s10565-019-09502-7. Epub 2019 Nov 22.
• [13] Effects of 1alpha,25 dihydroxyvitamin D3 and testosterone on miRNA and mRNA expression in LNCaP cells. Mol Cancer. 2011 May 18;10:58.
• [14] THC exposure of human iPSC neurons impacts genes associated with neuropsychiatric disorders. Transl Psychiatry. 2018 Apr 25;8(1):89. doi: 10.1038/s41398-018-0137-3.
• [15] Characterization of formaldehyde's genotoxic mode of action by gene expression analysis in TK6 cells. Arch Toxicol. 2013 Nov;87(11):1999-2012.
• [16] Mitochondrial Uncoupling Induces Epigenome Remodeling and Promotes Differentiation in Neuroblastoma. Cancer Res. 2023 Jan 18;83(2):181-194. doi: 10.1158/0008-5472.CAN-22-1029.
• [17] A transcriptomics-based in vitro assay for predicting chemical genotoxicity in vivo. Carcinogenesis. 2012 Jul;33(7):1421-9.
• [18] Toxicoproteomics reveals an effect of clozapine on autophagy in human liver spheroids. Toxicol Mech Methods. 2023 Jun;33(5):401-410. doi: 10.1080/15376516.2022.2156005. Epub 2022 Dec 19.
• [19] Bromodomain-containing protein 4 (BRD4) regulates RNA polymerase II serine 2 phosphorylation in human CD4+ T cells. J Biol Chem. 2012 Dec 14;287(51):43137-55.
• [20] Comprehensive analysis of transcriptomic changes induced by low and high doses of bisphenol A in HepG2 spheroids in vitro and rat liver in vivo. Environ Res. 2019 Jun;173:124-134. doi: 10.1016/j.envres.2019.03.035. Epub 2019 Mar 18.
• [21] From transient transcriptome responses to disturbed neurodevelopment: role of histone acetylation and methylation as epigenetic switch between reversible and irreversible drug effects. Arch Toxicol. 2014 Jul;88(7):1451-68.
• [22] Pleiotropic combinatorial transcriptomes of human breast cancer cells exposed to mixtures of dietary phytoestrogens. Food Chem Toxicol. 2009 Apr;47(4):787-95.
• [23] Sulforaphane-induced apoptosis in human leukemia HL-60 cells through extrinsic and intrinsic signal pathways and altering associated genes expression assayed by cDNA microarray. Environ Toxicol. 2017 Jan;32(1):311-328.